Xtandi 40 mg soft capsules
- Name:
Xtandi 40 mg soft capsules
- Company:
Astellas Pharma Co. Ltd
- Active Ingredients:
- Legal Category:
Product subject to medical prescription which may not be renewed (A)
Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 10/06/19
(Click to Download)Click on this link to Download PDF directly
Astellas Pharma Co. Ltd
Company Products
When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Updated on 10 June 2019 PIL
Reasons for updating
- Individual PILs superseded by joint PIL
Updated on 30 October 2018 PIL
Reasons for updating
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 3 - how to take/use
- Change to section 4 - possible side effects
- Change to section 6 - what the product contains
Updated on 30 October 2018 SmPC
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.1 - Therapeutic indications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 14 February 2018 PIL
Reasons for updating
- New PIL for new product
Updated on 14 February 2018 SmPC
Reasons for updating
- New SmPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 14 February 2018 SmPC
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.8 - Undesirable effects
- Change to section 9 - Date of first authorisation/renewal of the authorisation
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
2. Quantity of sorbitol updated in section 2(Qualitative and quantitative composition)
3. Information on initiation/supervision of treatment and administration with enzalutamide updated in Section 4.2(Posology and method of administration)
4. Date of last renewal updated to 08 Feb 2018 in section 9(date of first authorization/renewal)
5. Date of revision of the text updated to 08 Feb 2018 in section 10 (Date of revision of the text)
Updated on 14 February 2018 PIL
Reasons for updating
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
- Change to section 3 - how to take/use
- Change to section 3 - overdose, missed or forgotten doses
- Change to section 4 - possible side effects
- Change to section 5 - how to store or dispose
- Change to section 6 - what the product looks like and pack contents
- Change to section 6 - date of revision
Updated on 7 October 2017 SmPC
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Section 4.7
change from "may have" to "has" a moderate influence on the ability to drive and use machines
Section 4.8
Table of adverse drug reactions amended in terms of the order of presenting the entries
Section 10
Change in date of revision to 21 September 2017
Updated on 19 July 2017 SmPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated instruction on how to proceed in case of seizure added.
Section 4.8:
Information on the incidence of seizure observed in post authorization safety study added.
Section 5.1:
Overview of the clinical trials presented in section 5.1 and their results in terms of PSA decrease has been added to the start of section 5.1.
The results of clinical trial 9785-CL-0410 (enzalutamide post abiraterone in patients with metastatic CRPC) have been added to section 5.1.
Section 10:
The date of revision is amended to 09-June-2017
Updated on 21 March 2017 PIL
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 6 - date of revision
Updated on 16 March 2017 SmPC
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
The following text has been added:
This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant (see section 5.3).
It is not known if enzalutamide is present in human milk. Enzalutamide and/or its metabolites are secreted in rat milk (see section 5.3).
Section 5.1
The pharmacotherapeutic group and ATC have now been added:
Pharmacotherapeutic group: anti-androgen, hormone antagonists and related agents, ATC code: L02BB04
Section 5.3
The results from studies performed in pregnant and breastfeeding rats have been added to this section.
Section 10
Date of revision changed to 09 March 2017
Updated on 11 May 2016 PIL
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to date of revision
Updated on 11 May 2016 SmPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated to reflect the revised incidence of seizure following the addition of the data collected during the TERRAIN clinical study.
Section 5.1:
Addition of paragraph outlining the results of the TERRAIN study.
Section 10:
Date of revision changed to 01 April 2016
Updated on 7 December 2015 PIL
Reasons for updating
- Change to side-effects
- Change to drug interactions
- Change to date of revision
Updated on 4 December 2015 SmPC
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Section 4.8, table of adverse reactions has been updated to include diarrhoea and thrombocytopaenia with frequency unknown (observed from post-marketing experience).
Section 10, date of revision has been updated to 30 November 2015
Updated on 2 July 2015 SmPC
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
Hepatic impairment
No dose adjustment is necessary for patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B or C, respectively). An increased drug half-life has however been observed in patients with severe hepatic impairment (see section 4.4 and 5.2).
4.4 Special warnings and precautions for use
Severe hepatic impairment
An increased drug half-life has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction (see section 4.5) may be increased.
5.2 Pharmacokinetic properties
Hepatic impairment
Hepatic impairment did not have a pronounced effect on the total exposure to enzalutamide or its active metabolite. Drug half-life was however doubled in patients with severe hepatic impairment compared with healthy controls (10.4 days compared to 4.7 days), possibly related to an increased tissue distribution.
The pharmacokinetics of enzalutamide were examined in subjects with baseline mild (N = 6), moderate (N = 8) or severe (N=8) hepatic impairment (Child Pugh Class A , B or C, respectively) and in 22 matched control subjects with normal hepatic function. Following a single oral 160 mg dose of enzalutamide, the AUC and Cmax for enzalutamide in subjects with mild impairment increased by 5% and 24%, respectively, the AUC and Cmax of enzalutamide in subjects with moderate impairment increased by 29% and decreased by 11%, respectively, and the AUC and Cmax of enzalutamide in subjects with severe impairment increased by 5% and decreased by 41%, respectively, compared to healthy control subjects. For the sum of unbound enzalutamide plus the unbound active metabolite, the AUC and Cmax in subjects with mild impairment increased by 14% and 19%, respectively, the AUC and Cmax in subjects with moderate impairment increased by 14% and decreased by 17%, respectively, and the AUC and Cmax in subjects with severe hepatic impairment increased by 34% and decreased by 27%., respectively, compared to healthy control subjects.
The date of revision has been updated to June 2015
Updated on 9 June 2015 SmPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Section 4.4, the following text has been added:
Hypersensitivity reactions
Hypersensitivity reactions manifested by symptoms including, but not limited to, tongue oedema, lip oedema and pharyngeal oedema have been observed with enzalutamide (see section 4.8).
Section 4.8, the following has been added:
Immune system disorders not known*: tongue oedema, lip oedema, pharyngeal oedema
Gastrointestinal disorders not known*: nausea, vomiting
Skin and subcutaneous tissue disorders not known*: rash
Section 5.1 has been revised to include updated overall survival analysis data.
The date of revision has been updated to May 2015
Updated on 3 June 2015 PIL
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 27 April 2015 SmPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Section 4.4:
The following text has been added
Posterior reversible encephalopathy syndromeThere have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving Xtandi (see section 4.8). PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of Xtandi in patients who develop PRES is recommended.
Section 4.8:
The following has been added
Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients (see section 4.4).
|
Nervous system disorders |
very common: headache common: memory impairment, amnesia, disturbance in attention, restless legs syndrome uncommon: cognitive disorder, seizure not known*: posterior reversibile encephalopathy syndrome |
Section 10:
The date of revision has been updated to April 2015
Updated on 23 April 2015 PIL
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to date of revision
Updated on 3 February 2015 SmPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 6.3 - Shelf life
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Androgen deprivation therapy may prolong the QT interval
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Xtandi.
Section 4.5 updated to include the following:
Medicinal products which prolong the QT interval
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Xtandi with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
Section 4.8 updated to include the following:
Cardiac disorders not known**: QT-prolongation (see sections 4.4 and 4.5)
Section 6.3:
Shelf life extended to 3 years
Section 10:
Date of revision of text updated to January 2015
Updated on 30 January 2015 PIL
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to drug interactions
- Change to date of revision
Updated on 9 December 2014 SmPC
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
There are updates throughout the SPC with the following sections implicated:
Section 4.1 Therapeutic indications
Addition of new indication for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated (see section 5.1)
Section 4.2 Posology
Added: Medical castration with an LHRH analogue should be continued during treatment of patients not surgically castrated.
Section on Paediatric population updated
4.8 Undesirable effects
Updates throughout this section resulting from new data. Updated information on risk of seizure.
5.1 Pharmacodynamic properties
Clinical efficacy and safety
Information on the Prevail study added.
Added:
Older people: Of the 1671 patients in the phase 3 trials who received enzalutamide, 1261 patients (75%) were 65 years and over and 516 patients (31%) were 75 years and over. No overall differences in safety or effectiveness were observed between these older patients and younger patients.
10. Date of Revision of the Text
Changed to November 2014Updated on 3 December 2014 PIL
Reasons for updating
- Change to, or new use for medicine
- Change to warnings or special precautions for use
- Change to side-effects
- Change to further information section
- Change to date of revision
- Change to dosage and administration
Updated on 25 November 2014 SmPC
Reasons for updating
- Addition of black triangle
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated on 8 October 2014 PIL
Reasons for updating
- Change to side-effects
Updated on 7 October 2014 SmPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Musculoskeletal and connective tissue disorders:
common: fractures*
not known**: myalgia, muscle spasms, muscular weakness, back pain
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Updated on 21 February 2014 SmPC
Reasons for updating
- Change to Section 4.8 – Undesirable effects - how to report a side effect
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions after authorisation of the medicinal products is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via,
IMB Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
Updated on 20 December 2013 PIL
Reasons for updating
- New PIL for new product
Updated on 17 December 2013 SmPC
Reasons for updating
- New SPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)